Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573155 | SCV000667109 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-10 | criteria provided, single submitter | clinical testing | The p.R237P variant (also known as c.710G>C), located in coding exon 5 of the RAD51C gene, results from a G to C substitution at nucleotide position 710. The arginine at codon 237 is replaced by proline, an amino acid with dissimilar properties. In multiple assays testing RAD51C function, this alteration showed an abnormal read-out (Hu C et al. Cancer Res, 2023 Aug;83:2557-2571). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000816474 | SCV000956984 | uncertain significance | Fanconi anemia complementation group O | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 237 of the RAD51C protein (p.Arg237Pro). This variant is present in population databases (rs370393672, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 482163). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAD51C protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV001555922 | SCV001777415 | uncertain significance | not provided | 2020-07-08 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |